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US 2003/0195224 A1Published application
Oxazolo, thiazolo and selenazolo [4,5-c]-quinolin-4- amines and analogs thereof
Assignee3M Innovative Properties Company
InventorsJohn F. Gerster, Kyle J. Lindstrom, Gregory J. Marszalek, Bryon A. Merrill, John W. Mickelson, Michael J. Rice
Life of this patent
Estimating the term…
Abstract
Thiazolo-, oxazolo- and selenazolo[4,5-c]quinolin-4-amines and analogs thereof are described including methods of manufacture and the use of novel intermediates. The compounds are immunomodulators and induce cytokine biosynthesis, including interferon and/or tumor biosynthesis, necrosis factor, and inhibit the T-helper-type 2 immune response. The compounds are further useful in the treatment of viral and neoplastic diseases.
Claims25
A compound of the formula I:
- 68
- wherein:
- R1 is selected from the group consisting of oxygen, sulfur and selenium;
- R2 is selected from the group consisting of
- hydrogen;
- alkyl;
- alkyl-OH;
- haloalkyl;
- alkenyl;
- alkyl-X-alkyl;
- alkyl-X-alkenyl;
- alkenyl-X-alkyl;
- alkenyl-X-alkenyl;
- alkyl-N(R5)2;
- alkyl-N3;
- alkyl-O—C(O)—N(R5)2;
- heterocyclyl;
- alkyl-X-heterocyclyl;
- alkenyl-X-heterocyclyl;
- aryl;
- alkyl-X-aryl;
- alkenyl-X-aryl;
- heteroaryl;
- alkyl-X-heteroaryl;
- and
- alkenyl-X-heteroaryl;
- R3 and R4 are each independently:
- hydrogen;
- X-alkyl;
- halo;
- haloalkyl;
- N(R5)2;
- or when taken together, R3 and R4 form a fused aromatic, heteroaromatic, cycloalkyl or heterocyclic ring;
- X is selected from the group consisting of —O—, —S—, —NR5—, —C(O)—, —C(O)O—, —OC(O)—, and a bond;
- and
- each R5 is independently H or C1-8alkyl;
- with the proviso that when R1 is sulfur, R3 is not —NH2;
- or a pharmaceutically acceptable salt thereof.
35 more elements
2-n-propylthiazolo[4,5-c]quinolin-4-amine, or a pharmaceutically acceptable salt thereof.
A compound selected from the group consisting of:
- 2-methylthiazolo[4,5-c]quinolin-4-amine;
- thiazolo[4,5-c]quinolin-4-amine;
- 2-ethylthiazolo[4,5-c]quinolin-4-amine;
- 2-propylthiazolo[4,5-c]quinolin-4-amine;
- 2-pentylthiazolo[4,5-c]quinolin-4-amine;
- 2-butylthiazolo[4,5-c]quinolin-4-amine;
- 2-(1-methylethyl)thiazolo[4,5-c]quinolin-4-amine;
- 2-(2-phenyl-1-ethenyl)thiazolo[4,5-c]quinolin-4-amine;
- 2-(2-phenyl-1-ethyl)thiazolo[4,5-c]quinolin-4-amine;
- 2-(4-aminothiazolo[4,5-c]quinolin-2-yl)-1,1-dimethylethyl carbamate;
- 2-(ethoxymethyl)thiazolo[4,5-c]quinolin-4-amine;
- 2-(methoxymethyl)thiazolo[4,5-c]quinolin-4-amine;
- 2-(2-methylpropyl)thiazolo[4,5-c]quinolin-4-amine;
- 2-benzylthiazolo[4,5-c]quinolin-4-amine;
- 8-methyl-2-propylthiazolo[4,5-c]quinolin-4-amine;
- (4-aminothiazolo[4,5-c]quinolin-2-yl)methanol;
- 2-methyloxazolo[4,5-c]quinolin-4-amine;
- 2-ethyloxazolo[4,5-c]quinolin-4-amine;
- 2-butyloxazolo[4,5-c]quinolin-4-amine;
- 2-propylthiazolo[4,5-c]quinolin-4,8-diamine;
- 2-propyloxazolo[4,5-c]quinolin-4-amine;
- 8-bromo-2-propylthiazolo[4,5-c]quinolin-4-amine;
- 7-methyl-2-propylthiazolo[4,5-c]quinolin-4-amine;
- 2-butyl-7-methyloxazolo[4,5-c]quinolin-4-amine;
- 7-methyl-2-propyloxazolo[4,5-c]quinolin-4-amine;
- 7-fluoro-2-propyloxazolo[4,5-c]quinolin-4-amine;
- 7-fluoro-2-propylthiazolo[4,5-c]quinolin-4-amine;
- 2-propyl-7-(trifluoromethyl)thiazolo[4,5-c]quinolin-4-amine;
- 2-(4-morpholino)thiazolo[4,5-c]quinolin-4-amine;
- 2-(1-pyrrolidino)thiazolo[4,5-c]quinolin-4-amine;
- 2-butylthiazolo[4,5-c][1,5]naphthyridin-4-amine;
- 2-propylthiazolo[4,5-c][1,5]naphthyridin-4-amine;
- 7-chloro-2-propylthiazolo[4,5-c]quinolin-4-amine;
- 7-methoxy-2-propylthiazolo[4,5-c]quinolin-4-amine;
- and pharmaceutically acceptable salts thereof.
32 more elements
A pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I(a):
- 69
- wherein:
- R1 is selected from the group consisting of oxygen, sulfur and selenium;
- R2 is selected from the group consisting of
- hydrogen;
- alkyl;
- alkyl-OH;
- haloalkyl;
- alkenyl;
- alkyl-X-alkyl;
- alkyl-X-alkenyl;
- alkenyl-X-alkyl;
- alkenyl-X-alkenyl;
- alkyl-N(R5)2;
- alkyl-N3;
- alkyl-O—C(O)—N(R5)2;
- heterocyclyl;
- alkyl-X-heterocyclyl;
- alkenyl-X-heterocyclyl;
- aryl;
- alkyl-X-aryl;
- alkenyl-X-aryl;
- heteroaryl;
- alkyl-X-heteroaryl;
- and
- alkenyl-X-heteroaryl;
- R3 and R4 are each independently.
- hydrogen;
- X-alkyl;
- halo;
- haloalkyl;
- N(R5)2;
- or when taken together, R3 and R4 form a fused aromatic, heteroaromatic, cycloalkyl or heterocyclic ring;
- X is selected from the group consisting of —O—, —S—, —NR5—, —C(O)—, —C(O)O—, —OC(O)—, and a bond;
- and
- each R5 is independently H or C1-8alkyl;or a pharmaceutically acceptable salt thereof, with a pharmaceutically acceptable carrier.
33 more elements
A compound of the formula II:
- 70
- wherein
- R1 is selected from the group consisting of oxygen, sulfur and selenium;
- R2 is selected from the group consisting of
- hydrogen;
- alkyl;
- alkyl-OH;
- haloalkyl;
- alkenyl;
- alkyl-X-alkyl;
- alkyl-X-alkenyl;
- alkenyl-X-alkyl;
- alkenyl-X-alkenyl;
- alkyl-N(R5)2;
- alkyl-N3;
- alkyl-O—C(O)—N(R5)2;
- heterocyclyl;
- alkyl-X-heterocyclyl;
- alkenyl-X-heterocyclyl;
- aryl;
- alkyl-X-aryl;
- alkenyl-X-aryl;
- heteroaryl;
- alkyl-X-heteroaryl;
- alkenyl-X-heteroaryl;
- SO2CH3;
- and
- CH2—O—C(O)—CH3;
- R3 and R4 are each independently:
- hydrogen;
- X-alkyl;
- halo;
- haloalkyl;
- or when taken together, R3 and R4 form a fused aromatic, heteroaromatic, cycloalkyl or heterocyclic ring;
- X is selected from the group consisting of —O—, —S—, —NR5—, —C(O)—, —C(O)O—, and a bond;
- and
- each R5 is independently H or C1-8alkyl.
34 more elements
A compound selected from the group consisting of:
- 2-methylthiazolo[4,5-c]quinoline-5N-oxide;
- 2-ethylthiazolo[4,5-c]quinoline-5N-oxide;
- 2-propylthiazolo[4,5-c]quinoline-5N-oxide;
- 2-pentylthiazolo[4,5-c]quinoline-5N-oxide;
- 2-butylthiazolo[4,5-c]quinoline-5N-oxide;
- 2-(1-methyethyl)thiazolo[4,5-c]quinoline-5N-oxide;
- 2-(2-phenyl-1-ethenyl)thiazolo[4,5-c]quinoline-5N-oxide;
- 2-phenylethylthiazolo[4,5-c]quinoline-5N-oxide;
- 2-methyl-1-thiazolo[4,5-c]quinolin-2-yl-2-propanol-5N-oxide;
- 2-(ethoxymethyl)thiazolo[4,5-c]quinoline-5N-oxide;
- 2-(methoxymethyl)thiazolo[4,5-c]quinoline-5N-oxide;
- 2-(2-methylpropyl)thiazolo[4,5-c]quinoline-5N-oxide;
- 2-benzylthiazolo[4,5-c]quinoline-5N-oxide;
- 8-methyl-2-propylthiazolo[4,5-c]quinoline-5N-oxide;
- and
- 2-butyloxazolo[4,5-c]quinoline-5N-oxide.
13 more elements
Dependencies are inferred from the claim text.